1qf0

THERMOLYSIN (E.C.3.4.24.27) COMPLEXED WITH (2-SULPHANYL-3-PHENYLPROPANOYL)-PHE-TYR. PARAMETERS FOR ZN-BIDENTATION OF MERCAPTOACYLDIPEPTIDES IN METALLOENDOPEPTIDASE

spinqualitylabelsall models 1qf0, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1qf0 is a 1 chain structure with sequence from Bacillus thermoproteolyticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: CA, DMS, TI2, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function THER_BACTH Extracellular zinc metalloprotease. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Three alpha-mercaptoacyldipeptides differing essentially in the size of their C-terminal residues have been crystallized in the thermolysin active site. A new mode of binding was observed for 3 [HS-CH(CH(2)Ph)CO-Phe-Tyr] and 4 [HS-CH((CH(2))(4)CH(3))CO-Phe-Ala], in which the mercaptoacyl moieties act as bidentates with Zn-S and Zn-O distances of 2.3 and 2.4 A, respectively, the side chains fitting the S(1), S(1)', and S(2)' pockets. Moreover, a distance of 3.1 A between the sulfur atom and the OE1 of Glu(143) suggests that they are H-bonded and that one of these atoms is protonated. This H-bond network involving Glu(143), the mercaptoacyl group of the inhibitor, and the Zn ion could be considered a "modified" transition state mimic of the peptide bond hydrolysis. Due to the presence of the hindering (5-phenyl)proline, the inhibitor HS-CH(CH(2)Ph)CO-Gly-(5-Ph)Pro (2) interacts through the usual Zn monodentation via the thiol group and occupancy of S(1)' and S(2)' subsites by the aromatic moieties, the proline ring being outside the active site. The inhibitory potencies are consistent with these structural data, with higher affinities for 3 (4.2 x 10(-)(8) M) and 4 (4.8 x 10(-)(8) M) than for 2 (1.2 x 10(-)(6) M). The extension of the results, obtained with thermolysin being considered as the model of physiological zinc metallopeptidases, allows inhibitor-recognition modes for other peptidases, such as angiotensin converting enzyme and neutral endopeptidase, to be proposed and opens interesting possibilities for the design of new classes of inhibitors. Crystal structures of alpha-mercaptoacyldipeptides in the thermolysin active site: structural parameters for a Zn monodentation or bidentation in metalloendopeptidases.,Gaucher JF, Selkti M, Tiraboschi G, Prange T, Roques BP, Tomas A, Fournie-Zaluski MC Biochemistry. 1999 Sep 28;38(39):12569-76. PMID:10504225 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thermolysin 3D structures

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